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use crate::sbml::import::_convert_mathml_to_fn_update::sbml_transition_to_update_function;
use crate::sbml::import::_read_layout::read_sbml_layout;
use crate::sbml::import::_read_mathml::MathMl;
use crate::sbml::import::_read_species::{read_species, SbmlSpecie};
use crate::sbml::import::_read_transitions::{read_transitions, SbmlTransition};
use crate::sbml::Layout;
use crate::{BooleanNetwork, Monotonicity, RegulatoryGraph};
use regex::Regex;
use roxmltree::{ExpandedName, Node};
use std::collections::{HashMap, HashSet};
use std::convert::TryFrom;
const SBML: &str = "http://www.sbml.org/sbml/level3/version1/core";
const SBML_QUAL: &str = "http://www.sbml.org/sbml/level3/version1/qual/version1";
const SBML_LAYOUT: &str = "http://www.sbml.org/sbml/level3/version1/layout/version1";
const MATHML: &str = "http://www.w3.org/1998/Math/MathML";
mod _convert_mathml_to_fn_update;
mod _read_layout;
mod _read_mathml;
mod _read_species;
mod _read_transitions;
impl BooleanNetwork {
pub fn try_from_sbml(model_file: &str) -> Result<(BooleanNetwork, Layout), String> {
BooleanNetwork::try_from_sbml_strict(model_file, &mut Vec::new())
}
pub fn try_from_sbml_strict(
model_file: &str,
warnings: &mut Vec<String>,
) -> Result<(BooleanNetwork, Layout), String> {
let document =
roxmltree::Document::parse(model_file).map_err(|e| format!("XML Error: {:?}", e))?;
let root = document.root();
if root.children().count() == 0 {
return Err("Document is empty.".into());
}
if root.children().count() > 1 {
return Err("Document contains multiple top-level tags. Only SBML expected.".into());
}
let sbml = root.children().next().unwrap();
if sbml.tag_name().name() != "sbml" {
return Err("Root element is not <sbml>.".into());
}
if sbml.tag_name().namespace() != Some(SBML) {
return Err("The document does not use the SBML Level3 namespace.".into());
}
let requires_qual = sbml.attribute((SBML_QUAL, "required"));
if requires_qual != Some("true") {
warnings.push("This model does not declare SBML-qual as a requirement.".into());
}
let model = read_unique_child(sbml, (SBML, "model"))?;
let species = read_species(model)?;
let transitions = read_transitions(model)?;
for specie in &species {
if specie.max_level.is_some() && specie.max_level.unwrap() != 1 {
return Err(format!(
"Specie with ID {} is not Boolean (max level {}).",
specie.id,
specie.max_level.unwrap()
));
}
}
let specie_to_name = create_normalized_names(&species, warnings)?;
assert_eq!(specie_to_name.len(), species.len());
let mut names: Vec<String> = specie_to_name.values().cloned().collect();
names.sort();
let mut regulatory_graph = RegulatoryGraph::new(names);
create_regulations(&mut regulatory_graph, &transitions, &specie_to_name)?;
let mut boolean_network = BooleanNetwork::new(regulatory_graph);
for transition in &transitions {
if transition.default_term.is_some() {
for term in &transition.function_terms {
if let Some(math) = &term.math {
create_explicit_parameters(math, &mut boolean_network)?;
}
}
let out_var = &specie_to_name[&transition.outputs[0].qual_species];
let out_var = boolean_network.graph.find_variable(out_var).unwrap();
let update_function = sbml_transition_to_update_function(
&boolean_network,
transition,
&specie_to_name,
)?;
boolean_network.add_update_function(out_var, update_function)?;
}
}
let layout = read_sbml_layout(model);
let layout = match layout {
Ok(l) => l.glyphs,
Err(err) => {
warnings.push(err);
HashMap::new()
}
};
let mut transformed_layout: HashMap<String, (f64, f64)> = HashMap::new();
for (k, v) in &layout {
let var_name = specie_to_name.get(k);
if let Some(var) = var_name {
transformed_layout.insert(var.clone(), *v);
} else {
warnings.push(format!("Unknown layout glyph `{}`.", k));
}
}
Ok((boolean_network, transformed_layout))
}
}
fn read_unique_child<'a, 'input: 'a>(
parent: Node<'a, 'input>,
name: (&'static str, &'static str),
) -> Result<Node<'a, 'input>, String> {
let name = ExpandedName::from(name);
let mut tags = parent.children().filter(|node| node.tag_name() == name);
let fst = tags.next();
if let Some(fst) = fst {
let snd = tags.next();
if snd.is_none() {
Ok(fst)
} else {
Err(format!(
"Multiple {} found in {}.",
name.name(),
parent.tag_name().name()
))
}
} else {
Err(format!(
"Could not find tag {} in {}.",
name.name(),
parent.tag_name().name()
))
}
}
fn child_tags<'a, 'input: 'a>(
parent: Node<'a, 'input>,
name: (&'static str, &'static str),
) -> Vec<Node<'a, 'input>> {
let name = ExpandedName::from(name);
parent.children().filter(|n| n.tag_name() == name).collect()
}
fn create_normalized_names(
species: &[SbmlSpecie],
warnings: &mut Vec<String>,
) -> Result<HashMap<String, String>, String> {
let mut id_to_name = HashMap::new();
let mut name_to_id = HashMap::new();
let mut duplicates = HashSet::new();
let name_regex = Regex::new(r"[^a-zA-Z0-9_]").unwrap();
for specie in species {
let name = specie.name.clone().unwrap_or_else(|| specie.id.clone());
let normalized = name_regex.replace_all(&name, "_").to_string();
if normalized != name {
warnings.push(format!(
"Renamed `{}` to `{}`. Original name contains invalid symbols.",
name, normalized
));
}
if id_to_name
.insert(specie.id.clone(), normalized.clone())
.is_some()
{
return Err(format!("Duplicate specie ID found: `{}`", specie.id));
}
if let Some(previous) = name_to_id.insert(normalized.clone(), specie.id.clone()) {
duplicates.insert(previous);
duplicates.insert(specie.id.clone());
}
}
for duplicate_id in duplicates {
let specie = species
.iter()
.find(|s| s.id == duplicate_id)
.cloned()
.unwrap();
let current_name = &id_to_name[&specie.id];
let concat = format!("{}_{}", specie.id, current_name);
let mut updated_name = concat.clone();
let mut i = 0;
while name_to_id.contains_key(&updated_name) {
updated_name = format!("{}_{}", concat, i);
i += 1;
}
warnings.push(format!(
"Renamed `{}` to `{}` to avoid duplicates.",
current_name, updated_name
));
id_to_name.insert(specie.id.clone(), updated_name.clone());
}
Ok(id_to_name)
}
fn create_regulations(
rg: &mut RegulatoryGraph,
transitions: &[SbmlTransition],
id_to_var: &HashMap<String, String>,
) -> Result<(), String> {
for transition in transitions {
if transition.outputs.len() != 1 {
return Err(format!(
"Every transition can have only one output. `{}` has {}.",
transition.id,
transition.outputs.len()
));
}
let out_specie = &transition.outputs[0].qual_species;
let out_variable = id_to_var.get(out_specie);
if out_variable.is_none() {
return Err(format!(
"Unknown output specie `{}` used in transition `{}`.",
out_specie, transition.id
));
}
for input in &transition.inputs {
let in_id = &input.id;
let in_specie = &input.qual_species;
let in_variable = id_to_var.get(in_specie);
if in_variable.is_none() {
return Err(format!(
"Unknown input specie `{}` used in transition `{}`.",
in_specie, transition.id
));
}
let is_observable = if let Some(essential) = input.essential {
essential
} else {
transition.function_terms.iter().any(|t| {
t.math
.as_ref()
.map(|m| {
m.contains_identifier(in_specie)
|| in_id
.as_ref()
.map(|id| m.contains_identifier(id))
.unwrap_or(false)
})
.unwrap_or(false)
}) || transition.function_terms.is_empty()
};
let monotonicity = input.sign.as_ref().and_then(|sign| {
if sign == "positive" {
Some(Monotonicity::Activation)
} else if sign == "negative" {
Some(Monotonicity::Inhibition)
} else {
None
}
});
rg.add_regulation(
in_variable.unwrap(),
out_variable.unwrap(),
is_observable,
monotonicity,
)?;
}
}
Ok(())
}
fn create_explicit_parameters(math: &MathMl, network: &mut BooleanNetwork) -> Result<(), String> {
match math {
MathMl::Boolean(_) => Ok(()),
MathMl::Integer(_) => Ok(()),
MathMl::Identifier(_) => Ok(()),
MathMl::Apply(_, args) => {
for a in args {
create_explicit_parameters(a, network)?;
}
Ok(())
}
MathMl::SymbolApply(name, args) => {
if let Some(p) = network.find_parameter(name) {
let current = network.get_parameter(p).get_arity();
if current != u32::try_from(args.len()).unwrap() {
return Err(format!(
"Parameter `{}` is used with cardinality {} as well as {}",
name,
current,
args.len()
));
}
} else {
network.add_parameter(name, u32::try_from(args.len()).unwrap())?;
}
for a in args {
create_explicit_parameters(a, network)?;
}
Ok(())
}
}
}
#[cfg(test)]
mod tests {
use crate::{BooleanNetwork, Monotonicity};
use pretty_assertions::assert_eq;
use std::collections::HashMap;
use std::convert::TryFrom;
#[test]
fn test() {
let model =
std::fs::read_to_string("sbml_models/g2a.sbml").expect("Cannot open result file.");
let (actual, layout) = BooleanNetwork::try_from_sbml(model.as_str()).unwrap();
let mut expected_layout = HashMap::new();
expected_layout.insert("CtrA".to_string(), (419.0, 94.0));
expected_layout.insert("GcrA".to_string(), (325.0, 135.0));
expected_layout.insert("DnaA".to_string(), (374.0, 224.0));
expected_layout.insert("CcrM".to_string(), (462.0, 222.0));
expected_layout.insert("SciP".to_string(), (506.0, 133.0));
let expected = BooleanNetwork::try_from(
"
CtrA -> CtrA
GcrA -> CtrA
CcrM -| CtrA
SciP -| CtrA
CtrA -| GcrA
DnaA -> GcrA
CtrA -> DnaA
GcrA -| DnaA
DnaA -| DnaA
CcrM -> DnaA
CtrA -> CcrM
CcrM -| CcrM
SciP -| CcrM
CtrA -> SciP
DnaA -| SciP
$CtrA: ((false | ((((!CtrA & GcrA) & !CcrM) & !SciP) & true)) | ((CtrA & !CcrM) & !SciP))
$GcrA: (!CtrA & DnaA)
$DnaA: (((CtrA & !GcrA) & !DnaA) & CcrM)
$CcrM: ((CtrA & !CcrM) & !SciP)
$SciP: (CtrA & !DnaA)
",
)
.unwrap();
assert_eq!(actual, expected);
assert_eq!(layout, expected_layout);
}
#[test]
fn test_name_resolution() {
let model = std::fs::read_to_string("sbml_models/g2a_with_names.sbml")
.expect("Cannot open result file.");
let (actual, layout) = BooleanNetwork::try_from_sbml(model.as_str()).unwrap();
let mut expected_layout = HashMap::new();
expected_layout.insert("CtrA___".to_string(), (419.0, 94.0));
expected_layout.insert("GcrA".to_string(), (325.0, 135.0));
expected_layout.insert("DnaA".to_string(), (374.0, 224.0));
expected_layout.insert("CcrM".to_string(), (462.0, 222.0));
expected_layout.insert("SciP".to_string(), (506.0, 133.0));
let expected = BooleanNetwork::try_from(
"
CtrA___ -> CtrA___
GcrA -> CtrA___
CcrM -| CtrA___
SciP -| CtrA___
CtrA___ -| GcrA
DnaA -> GcrA
CtrA___ -> DnaA
GcrA -| DnaA
DnaA -| DnaA
CcrM -> DnaA
CtrA___ -> CcrM
CcrM -| CcrM
SciP -| CcrM
CtrA___ -> SciP
DnaA -| SciP
$CtrA___: ((((!CtrA___ & GcrA) & !CcrM) & !SciP) | ((CtrA___ & !CcrM) & !SciP))
$GcrA: (!CtrA___ & DnaA)
$DnaA: (((CtrA___ & !GcrA) & !DnaA) & CcrM)
$CcrM: ((CtrA___ & !CcrM) & !SciP)
$SciP: (CtrA___ & !DnaA)
",
)
.unwrap();
assert_eq!(actual, expected);
assert_eq!(layout, expected_layout);
}
#[test]
fn test_cell_collective() {
let model = std::fs::read_to_string("sbml_models/cell_collective_vut.sbml")
.expect("Cannot open result file.");
let (actual, layout) = BooleanNetwork::try_from_sbml(model.as_str()).unwrap();
assert_eq!(actual.graph.num_vars(), 66);
assert_eq!(actual.graph.regulations.len(), 139);
assert_eq!(layout.len(), actual.graph.num_vars());
assert!(actual.graph.find_variable("glucose").is_some());
assert!(actual.graph.find_variable("lactic_acid").is_some());
assert_eq!(
actual
.graph
.find_regulation(
actual.graph.find_variable("sigG").unwrap(),
actual.graph.find_variable("sigK").unwrap(),
)
.unwrap()
.monotonicity,
Some(Monotonicity::Activation)
)
}
#[test]
fn test_apoptosis_stable() {
let model = std::fs::read_to_string("sbml_models/apoptosis_stable.sbml")
.expect("Cannot open result file.");
let (actual, layout) = BooleanNetwork::try_from_sbml(model.as_str()).unwrap();
assert_eq!(layout.len(), actual.graph.num_vars());
assert!(actual.graph.find_variable("Apoptosome_complex").is_some());
assert!(actual.graph.find_variable("FAS_FASL_complex").is_some());
assert!(actual.graph.find_variable("sa19_CASP9_Cytoplasm").is_some());
assert!(actual.graph.find_variable("sa47_CASP9_Cytoplasm").is_some());
}
#[test]
fn test_hmox_pathway() {
let model = std::fs::read_to_string("sbml_models/hmox1_pathway.sbml")
.expect("Cannot open result file.");
let (actual, layout) = BooleanNetwork::try_from_sbml(model.as_str()).unwrap();
assert_eq!(layout.len(), actual.graph.num_vars());
}
#[test]
fn test_apoptosis_network() {
let model = std::fs::read_to_string("sbml_models/apoptosis_network.sbml")
.expect("Cannot open result file.");
let (actual, layout) = BooleanNetwork::try_from_sbml(model.as_str()).unwrap();
assert_eq!(actual.graph.num_vars(), 41);
assert_eq!(layout.len(), 0);
}
#[test]
fn diff_test() {
let benchmarks = std::fs::read_dir("./sbml_models/real_world").unwrap();
for bench_dir in benchmarks {
let bench_dir = bench_dir.unwrap();
println!("Started {}", bench_dir.path().display());
if !bench_dir.file_type().unwrap().is_dir() {
eprintln!("SKIP: {} is not a directory.", bench_dir.path().display());
continue;
}
let sbml_model_path = bench_dir.path().join("model.sbml");
let model_string = std::fs::read_to_string(sbml_model_path).unwrap();
let model = BooleanNetwork::try_from_sbml(&model_string);
let sbml_model = match model {
Err(err) => {
eprintln!(
"ERROR: Invalid SBML model in {}.",
bench_dir.path().display()
);
panic!("{}", err);
}
Ok((model, _)) => model,
};
let aeon_model_path = bench_dir.path().join("model.aeon");
let model_string = std::fs::read_to_string(aeon_model_path).unwrap();
let aeon_model = BooleanNetwork::try_from(model_string.as_str()).unwrap();
assert_eq!(aeon_model.graph.num_vars(), sbml_model.graph.num_vars());
for v in aeon_model.graph.variables() {
print!("..{}..", aeon_model.graph.get_variable(v).name);
assert_eq!(
aeon_model.graph.get_variable(v),
sbml_model.graph.get_variable(v)
);
assert_eq!(
aeon_model.graph.regulators(v),
sbml_model.graph.regulators(v)
);
assert_eq!(
aeon_model.get_update_function(v),
sbml_model.get_update_function(v)
);
for reg in aeon_model.graph.regulators(v) {
let r1 = aeon_model.graph.find_regulation(reg, v).unwrap();
let r2 = sbml_model.graph.find_regulation(reg, v).unwrap();
assert_eq!(r1, r2);
}
}
println!();
println!("Finished {}", bench_dir.path().display());
}
}
}